Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

HGG Adv. 2024 Jul 18;5(3):100300. doi: 10.1016/j.xhgg.2024.100300. Epub 2024 Apr 26.

Abstract

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Keywords: COVID-19; HLA; association; asymptomatic infection; population stratification.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Asymptomatic Infections*
  • COVID-19* / genetics
  • COVID-19* / immunology
  • Female
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • SARS-CoV-2* / immunology

Substances

  • HLA Antigens